I know the Georgetown clinical trial for Tasigna is now FDA approved and moving ahead, but apparently it is limited to PWP living within 50 miles of DC, so...

I'm wondering: if you could find a doc willing to script Tasigna for you on an off-label basis, would you pursue that? If not, why not?

Would I take Tasigna (nilotinib) on an off-label basis?

Good question.

No. The weakness of the clinical trial results and the high price of nilotinib would stop me from using it.

Price affects me in two ways: the direct effect, I can't afford it, and an indirect effect, I have less confidence in results that come from trials of therapies which have a large profit potential.

The phase 1 clinical trial described by PDF [1] was small (12 participants). It may be just bad luck, but one participant had a heart attack, which PDF describes as "a known potential side effect of the drug". The results were not outstanding:
"... seven of the 12 did show some benefit. When all study participants were considered, the average improvement was between three to four points on a commonly used rating scale (approximately an eight percent improvement), while a five point change is generally viewed as the minimal improvement to make a difference in PD."

Reference:

[1] "Cancer Drug Shows Evidence of Safety for Parkinson’s"
Parkinson's Disease Foundation- Jul 11 2016
Cancer Drug Shows Evidence of Safety for Parkinson’s - Parkinson's Disease Foundation (PDF)

John

I searched the internet looking for a report of someone who is using nilotinib off label with favorable results. Outrside of the GT trial, I haven't been able to find any. I know some pwp must have tried nilotinib, but if so they don't seem inclined to report.

The answer right now is an absolute NO. I do not recommend starting Tasigna (Nilotinib) off-label at this time, unless the administering medical team included a neurologist, oncologist and cardiologist. This is a drug used for the treatment of CML cancer. It is not one to be used haphazardly. The good news is that the drug has been used for many years now as a cancer treatment, so we have very good safety/side effect data, and there is no reason to believe that the side effects would be worse at a lower dosage in PD patients. However, the most significant side effect, for which the FDA required Novartis to issue a Black Box warning, is possible life-threatening heart problems that may lead to an irregular heartbeat and possible sudden death. This problem is particularly prevalent for people who have QT prolongation, a condition involving heart wave intervals and rhythms. You need to be properly monitored before and during use. There are also possible interactions with other drugs, including MAO-b inhibitors, as well as with low blood potassium or magnesium. My point is that this is not a drug to take casually. It is much more serious a consideration than one may have, for example, in using Isradipine off-label.

That all being said, I believe the Georgetown phase I proof-of-concept study certainly indicates the need for further research. Although the study was small, poorly designed and open label, there was more than enough positive results to suggest the drug has symptomatic benefits, and possibly interventional disease modifying benefits. This is particularly true with the biomarker data, which you wouldn't think would be influenced to any great extent by a placebo effect. The results on the 6 month change in total UPDRS scores were significant, although certainly somewhat erratic. Even to John's point regarding what he quoted as a relatively small increase in UPDRS score was important. The reference he is using about needing a five point change in score to have practical significance for a patient is one that is used for symptomatic treatments, and wouldn't necessarily be the case for a longer term study of an interventional treatment. Keep in mind, the scores for these patients would have been anticipated to INCREASE by approximately 5 points over the 6 months (based on comparable results from the PPMI study for mid to late stage patients). In fact, it would be significant information even if there is no change in UPDRS over a long time period, which would imply the slowing or stopping of progression.

So, in the whole, the study results were certainly strong enough to support a PWP making the decision to go into the next phase of the research, if not actually take the drug unmonitored and off-label. What i would suggest at this time is wait for the larger, multi-centered trial, funded by MJFF/CPT/Van Andel, to get underway next year. If you qualify under the inclusion criteria, then you can get the drug for free with proper monitoring, while helping the whole PD community by being a trial volunteer.

By the way, another problem in drawing too much inference from the small GT trial was that them majority of their volunteers were dementia patients, not PD. The newer trials will only focus on PD.

I have spoken with a number of PWP who are taking nilotinib off-label. The large majority have said they are seeing improvement, some more than others. One person said they had to stop because of side effects.

Thanks everyone for your input. We have carefully read the study results from the Georgetown trial and what we got from it was this:

1. two participants withdrew: one because of increased caregiver burden (which is a non-issue to us) and the other apparently had a previously undiagnosed heart issue which was missed on the initial screening. You would certainly want to see a cardiologist before trying this drug to make sure you didn't have any unknown heart issues, and be monitored while on it....

2. with the exception of the participant who withdrew (patient NIL-12), the UPDRS and cognitive scores of 5 of the 6 participants who received the 300mg dose began improving within two months (most began improving earlier) and continued improvement through to week 24 when Tasigna administration was discontinued. The sixth patient who received 300mg ended the 24-week period at the same UPDRS-III score as he/she had at baseline (patient NIL-03, whose score was 12, so no further deterioration which is an improvement in and of itself), and had actually improved on the UPDRS-1-IV score (33 down to 28).

We think that, like many drugs, Tasigna will have no benefit for some PWP but will be life-changing for others. Mirapex, Azilect, and others provide relief for many PWP: yet others cannot tolerate them or worse, suffer horrific side effects.

If anyone knows or has heard of a doc who will script this for PD, please PM me

I personally believe trying Tasigna is worth the risk. At the rate my PD is progressing I certainly don't have 10 years to wait for this drug to be approved for Parkinson's disease. That being said, I plan to see if I can get my neurologist to prescribe Tasigna. This is something that I've been thinking of doing for awhile. In my case I have nothing to lose, and possibly everything to gain.

Alan Hoffman, one of the participants in the first GU nilotinib trial for PD, has just added a new post to his blog.

Towards the end of the post (2nd last paragraph) he makes reference to Tasigna (which he is taking).

The Continuing Saga of an Adventurous Life with Parkinson's Disease